Hypogonadal men with type 2 diabetes mellitus have smaller bone size and lower bone turnover

Colleluori, Georgia; Aguirre, Lina; Dorin, Richard I.; Robbins, David; Blevins, Dean; Barnouin, Yoann; Chen, Rui; Qualls, Clifford; Villareal, Dennis T.; Armamento-Villareal, Reina

doi:10.1016/j.bone.2017.03.039

Cited by 30 publications

(36 citation statements)

References 44 publications

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“…The bone area at the proximal femur and femoral shaft are most relevant for hip fracture risk which is the most devastating fracture. T2DM was associated with a smaller cross-sectional area at the tibia and radius (men and women n = 1069) [ 10 ], smaller cortical area of the tibia (25 postmenopausal women with T2DM and 25 controls) [ 24 ] and lower endosteal and periosteal circumferences and total area at the tibia (hypogonadal males n = 105) [ 25 ]. In addition to measuring bone area at peripheral sites, these studies were conducted in relatively small and specific populations, potentially restricting the generalizability of the results.…”

Section: Discussionmentioning

confidence: 99%

Type 2 Diabetes in Relation to Hip Bone Density, Area, and Bone Turnover in Swedish Men and Women: A Cross-Sectional Study

et al. 2018

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Men and women with type 2 diabetes mellitus (T2DM) have higher risk of hip fracture, but the mechanisms are not fully understood. We aimed to investigate how T2DM, glucose, and insulin were associated with femoral bone mineral density (BMD), bone mineral area (BMA), and bone turnover markers. We used two cross-sectional cohorts: the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 452, mean age 82 years) and the Swedish Mammography Cohort Clinical (SMCC, n = 4713, mean age 68 years). We identified men and women with normal fasting glucose (NFG), impaired fasting plasma glucose (IFG), and T2DM. BMD and BMA at the total hip and femoral shaft were measured using dual energy X-ray absorptiometry (DXA). Bone turnover markers; CrossLaps and osteocalcin were measured in women. Linear regression models were applied. Men and women showed a progressively higher BMD following the clinical cutoffs of fasting glucose from NFG to IFG to T2DM. In contrast, there was a progressively lower BMA. Men and women with T2DM, compared to those with NFG, had lower BMA at the total hip (− 1.7%; 95% CI − 3.2, − 0.2 and − 1.0%; 95% CI − 1.6, − 0.4) and the femoral shaft (− 2.0%; 95% CI − 3.5, − 0.4 and − 0.6%; 95% CI − 1.2, − 0.01), respectively. T2DM was associated with lower concentrations of CrossLaps (− 8.1%; 95% CI − 12.7, − 3.6) and osteocalcin (− 15.2%; 95% CI − 19.0, − 11.2). These cross-sectional results indicate that those with T2DM have smaller bone area and lower bone turnover, which could increase the risk of hip fracture.Electronic supplementary materialThe online version of this article (10.1007/s00223-018-0446-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Type 2 Diabetes in Relation to Hip Bone Density, Area, and Bone Turnover in Swedish Men and Women: A Cross-Sectional Study

et al. 2018

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“…This study includes 105 subjects who participated in a single-arm clinical trial (gov Identifier: NCT01378299) investigating the pharmacogenetics of response to T therapy in HG men [ 11 , 12 ]. This particular report consists of the data collected in the first 6 months of the study.…”

Section: Methodsmentioning

confidence: 99%

“…The study population was divided into 4 categories based on baseline E2 levels (pg/mL): (1) <10; (2) 10.0–15.9; (3) 16.0–19.9; (4) ≥20.0 (first analysis) to establish the impact of different E2 levels on body composition, subcutaneous adipose tissue’s ESR1 expression at baseline, and in response to T therapy. As reported in Section 2.1 , this is a secondary analysis of a study investigating the pharmacogenetics of response to testosterone therapy among HG men [ 11 , 12 ]. Original sample power calculation was performed in order to detect significant differences in the primary outcome of the main project.…”

Section: Methodsmentioning

confidence: 99%

Adipocytes ESR1 Expression, Body Fat and Response to Testosterone Therapy in Hypogonadal Men Vary According to Estradiol Levels

et al. 2018

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Estradiol (E2), mainly produced from Testosterone (T) in men, promotes visceral lipolysis. However, high visceral fat and hyperestrogenemia are features of obese hypogonadal (HG) men. Our study objectives are to evaluate relationships between circulating E2 and: (1) fat mass; (2) Estrogen Receptor α (ESR1) expression in subcutaneous adipose tissue; (3) changes in body fat after 6 months (M) of T therapy in HG men. Hypotheses: (1) existence of a range of circulating E2 associated with better body composition; (2) serum E2 determines tissue E2 sensitivity which affects response to T therapy. Men 40–74 years old, T < 300 (ng/dL), given T-cypionate for 6 months. Subjects were divided into 4-E2 categories: (1) <10.0; (2) 10.0–15.9; (3) 16.0–19.9; (4) ≥20.0 (pg/mL). Body composition (DXA), fat biopsies (liposuction), gene expression (qPCR), serum E2 and T (LC/MS), at baseline and 6 months. We enrolled 105 men; 90 completed the study. Group 2 had lower total and truncal fat mass (p < 0.01) but higher % lean mass (p < 0.001). ESR1 mRNA was the highest in group 1 (p = 0.01). At 6 months, group 1 had higher reduction in total (p = 0.03) and truncal (p = 0.01) fat. In conclusion, serum E2 = 10–15.9 (pg/mL) is associated with the best body composition profile in HG men; however, those with E2 < 10 (pg/mL) had the best response (greater fat loss) to T replacement possibly because of greater E2 sensitivity.

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“…type I procollagen-N-propeptide (PINP)). Hypogonadal men with type 2 diabetes have smaller bone size and lower bone turn over 8 . We conducted this analysis to study the effect of soy isoflavone supplementation on BTMs in men with T2DM and low testosterone levels (<12 nmol/L).…”

Section: Introductionmentioning

confidence: 99%

Effect of soy on bone turn-over markers in men with type 2 diabetes and hypogonadism – a randomised controlled study

Sathyapalan

Aye

Rigby

et al. 2017

Sci Rep

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Type 2 diabetes (T2DM) is associated with increased risk of fractures. Soy supplementation has been shown to have a beneficial effect on bone turnover markers (BTM) in postmenopausal women. However, the effect of soy supplementation on BTM in T2DM and particularly in men is unclear. We performed an analysis of a randomized double blind parallel study of 200 men with T2DM treated with soy, either with or without isoflavones. Outcome measures were type I collagen crosslinked beta C-telopeptide (βCTX), and type 1 procollagen-N-propeptide (P1NP). The men, with a total testosterone <12 nmol/L, were treated with 15 g soy protein containing 66 mg of isoflavones (SPI) or 15 g soy protein alone without isoflavones (SP) daily for three months. There was a 15% reduction in βCTX after three months of SPI compared to SP supplementation. There was no significant difference in P1NP with either SPI or SP supplementation. There was a significant linear correlation between the reduction in βCTX in the SPI group with the reduction in HbA1c (r 2 = 0.42; p = 0.04) and HOMA-IR (r 2 = 0.54; p = 0.02). Our study indicates that there was a significant reduction in bone resorption following 3 months of SPI supplementation that correlated with an improvement of glycemic control in men with T2DM.There is substantial epidemiological evidence that people with T2DM has increased risk of fractures 1,2 . This increase in fracture risk occurs despite bone mineral density (BMD) being comparatively higher in those with T2DM than those without. In a meta-analysis, Vestergaard reported an increased Z-score of 0.41 at the spine and 0.27 at the hip associated with T2DM 2 . T2DM has been shown to be an independent risk factor for fractures, which is not attributable to increased body mass index (BMI) or other classical osteoporosis risk factors 3 .Testosterone is anabolic for bone primarily through its aromatization to estrogen in adipose tissue 4 . Low testosterone in the setting of low or inappropriately normal luteinizing hormone and follicle-stimulating hormone is common in the diabetes population and may contribute to impaired bone strength in these men with T2DM 5 .Production and consumption of soy foods within Western countries have increased dramatically with postulated health benefits including improvement in bone health, especially in women 6 . Habitual intake of soy isoflavones has also been associated with a reduced risk of T2DM and cardiovascular disease (CVD) 7 .Bone turnover markers (BTMs) are biomarkers for fracture risk that have been used for the evaluation of effects of osteoporosis treatments, and include both bone resorption markers (e.g. type I collagen crosslinked Beta C-telopeptide (βCTX)) and bone formation markers (e.g. type I procollagen-N-propeptide (PINP)). Hypogonadal men with type 2 diabetes have smaller bone size and lower bone turn over 8 . We conducted this analysis to study the effect of soy isoflavone supplementation on BTMs in men with T2DM and low testosterone levels (<12 nmol/L).

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Hypogonadal men with type 2 diabetes mellitus have smaller bone size and lower bone turnover

Abstract: Among hypogonadal men, those with T2D have higher BMD, poorer bone geometry and relatively suppressed bone turnover. Studies with larger sample size are needed to verify our findings and possible even greater risk for fractures among hypogonadal diabetic men.

Cited by 30 publications

References 44 publications

Type 2 Diabetes in Relation to Hip Bone Density, Area, and Bone Turnover in Swedish Men and Women: A Cross-Sectional Study

Type 2 Diabetes in Relation to Hip Bone Density, Area, and Bone Turnover in Swedish Men and Women: A Cross-Sectional Study

Adipocytes ESR1 Expression, Body Fat and Response to Testosterone Therapy in Hypogonadal Men Vary According to Estradiol Levels

Effect of soy on bone turn-over markers in men with type 2 diabetes and hypogonadism – a randomised controlled study

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